DESCRIPTION: (Scanned from the applicant's abstract) Ground based and in-flight investigations illustrate changes in insulin, glucose, and amino acid metabolism during spaceflight. These observations may relate to altered pancreatic endocrine function which is insufficient to meet the needs of microgravity induced insulin resistance, and altered amino acid metabolism. The changes observed include decreased glucose tolerance, increased circulating insulin, and increased reliance upon glucose in muscles. The metabolic milieu resembles an insulin resistant syndrome, accompanied by a compensatory increase in pancreatic insulin secretion. However, the increase in insulin secretion is insufficient to ameliorate muscle atrophy. The increased insulin secretion is well correlated to muscle atrophy in spaceflight. There is not much known about the effects of microgravity on the other islet hormones glucagon and somatostatin. Both are key players in islet and metabolic physiology. Countermeasures which could modulate insulin, glucagon and somatostatin secretion in a compensatory manner to overcome insulin resistance and promote amino acid uptake by peripheral musculature might decrease muscle atrophy and reduce injury following re-adaptation to unit gravity. We hypothesize that human pancreatic islets of Langerhans have an increased requirement for amino acids in microgravity. We further hypothesize, that supplementation with specific additional amino acids will augment, enhance and normalize insulin secretion, when spaceflight paradigm stressors known to decrease insulin secretion, are applied. Our specific aims in this study are to: 1) assess the effect of a microgravity model cell culture system on basal endocrine secretory function and amino acid requirements in human islets of Langerhans, and 2) determine human islet endocrine function while testing amino acid countermeasures in the microgravity model. It is anticipated that these studies will further refine our understanding of human pancreatic amino acid requirements and endocrine regulation; phenomenon which may be limiting to extended-duration spaceflight missions. These studies will test countermeasures to augment pancreatic endocrine function, while considering both insulin and glucagon production in a way that will involve supplementation of diet with additional amino acids. These measures are ultimately aimed at improving spaceflight induced muscle atrophy, and ameliorating current re-adaptatinn constraints.